The global objective of this Mentored Clinical Scientist Research Career Development Award is to facilitate the development of the Candidate as an academic physician-scientist and to ensure his transition to independence. In light of these goals, the Candidate and his Mentor have designed an integrated plan that includes a strong foundation of didactic instruction in the field of molecular microbiology, combined with an intensive research component. The didactic component of his training will be directed by the experienced faculty at UT Southwestern, and will help to establish and foster a solid understanding of the important scientific principles and thought processes necessary for independence as an investigator. The Candidate will also receive training in cutting-edge and advanced scientific techniques in the laboratory of the Mentor and the Department of Microbiology. The Candidate's research progress and career development will be assessed and guided by a Mentoring Committee composed of established and successful physician-scientists at the Candidate's institution. The proposed award will provide the Candidate with the resources, training, and skills necessary for successful development into an independent physician-scientist. His career development plan fully addresses areas that are key to his successful growth, and this institution has committed to protect 80% of his time for these activities. The Candidate has successfully implemented a model for the study of nasopharyngeal colonization by Moraxella catarrhalis in the chinchilla. For the first time, the use of this model system will allow for the study of M. catarrhalis gene products expressed in vivo. In the first Specific Aim, DNA microarray technology will be utilized to identify M. catarrhalis genes that are induced or up-regulated during growth in the chinchilla nasopharynx. Mutant analysis will be used in the second Specific Aim to determine which of these gene products is essential for survival of this organism in the chinchilla nasopharynx. Finally, in the third Specific Aim, selected M. catarrhalis proteins which are determined to be exposed on the surface of this bacterium will be used as experimental immunogens to evaluate their ability to vaccinate against nasopharyngeal colonization in this animal model. Moraxella catarrhalis is a bacterial pathogen that is an important cause of respiratory tract disease in adults with certain preexisting conditions (i.e., chronic obstructive pulmonary disease) and in babies and very young children (i.e., ear infections). Information obtained from this research will identify components of this bacterium that have the potential to be developed into a vaccine to protect against M. catarrhalis disease.